全文获取类型
收费全文 | 298篇 |
免费 | 47篇 |
国内免费 | 1篇 |
专业分类
346篇 |
出版年
2022年 | 11篇 |
2021年 | 18篇 |
2020年 | 9篇 |
2019年 | 7篇 |
2018年 | 8篇 |
2017年 | 8篇 |
2016年 | 12篇 |
2015年 | 15篇 |
2014年 | 15篇 |
2013年 | 8篇 |
2012年 | 13篇 |
2011年 | 16篇 |
2010年 | 9篇 |
2009年 | 10篇 |
2008年 | 11篇 |
2007年 | 13篇 |
2006年 | 15篇 |
2005年 | 12篇 |
2004年 | 13篇 |
2003年 | 11篇 |
2002年 | 11篇 |
2001年 | 4篇 |
1999年 | 8篇 |
1998年 | 3篇 |
1997年 | 6篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 6篇 |
1991年 | 2篇 |
1989年 | 3篇 |
1984年 | 2篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1977年 | 2篇 |
1975年 | 2篇 |
1974年 | 5篇 |
1973年 | 2篇 |
1972年 | 4篇 |
1971年 | 3篇 |
1970年 | 2篇 |
1968年 | 2篇 |
1963年 | 2篇 |
1960年 | 3篇 |
1946年 | 1篇 |
1945年 | 2篇 |
1943年 | 2篇 |
1941年 | 2篇 |
1889年 | 1篇 |
排序方式: 共有346条查询结果,搜索用时 15 毫秒
91.
Shankar Venkatraman Alec D. Lebsack Kenneth Alves Michael F. Gardner Joyce James Russell B. Lingham Salony Maniar Richard A. Mumford Qian Si Nicholas Stock Kelly M. Treonze Bowei Wang Jasmine Zunic Benito Munoz 《Bioorganic & medicinal chemistry letters》2009,19(19):5803-5806
A series of prolyl-N-isonicotinoyl-(L)-4-aminophenylalanine derivatives substituted at the proline 4-position with cyclic amines was evaluated as VLA-4 antagonists. The ring size and presence or absence of fluorine affected potency and receptor occupancy. The analog with 3,3-difluoropiperidine at the proline 4-position (13) was the most potent compound and had very good duration of receptor occupancy in vitro. The ethyl ester prodrug of 13 demonstrated excellent receptor occupancy after oral dosing in rats. 相似文献
92.
Evaluation of the Australian weed risk assessment system for the prediction of plant invasiveness in Canada 总被引:1,自引:0,他引:1
The Australian Weed Risk Assessment system has been tested in a number of countries and geographical areas since its introduction
in 1997, and is widely considered to be an accurate method of predicting the risk of invasiveness of new plant introductions.
We evaluated the system against 152 plant species with at least a 50-year introduction history in Canada, including major
and minor weeds and species which have not naturalized. Four questions that referred explicitly to Australian conditions were
replaced with appropriate equivalent questions for Canada. The weediness of each species was independently rated by a panel
of Canadian agricultural, botanical, and conservation experts. Using the standard cut-off scores, the system correctly rejected
all major and 86% of minor weeds. However, it also incorrectly rejected 44% of non-weedy species. The diagnostic power of
the system, as measured by the receiver operating characteristic curve, was similar to but somewhat lower than that found
in other regions where the system has been evaluated. Answers to 23 of the 49 questions were not significantly associated
with experts’ weediness ratings, indicating that a simplified system could give equally reliable results for Canada. Experts’
ratings were strongly related to cold-hardiness, suggesting that the system could be improved by making better use of data
on climatic tolerances. We suggest that performance would also be improved by combining likelihood- and consequence-related
scores in a multiplicative rather than additive way. 相似文献
93.
Ghazalpour A Doss S Zhang B Wang S Plaisier C Castellanos R Brozell A Schadt EE Drake TA Lusis AJ Horvath S 《PLoS genetics》2006,2(8):e130
Systems biology approaches that are based on the genetics of gene expression have been fruitful in identifying genetic regulatory loci related to complex traits. We use microarray and genetic marker data from an F2 mouse intercross to examine the large-scale organization of the gene co-expression network in liver, and annotate several gene modules in terms of 22 physiological traits. We identify chromosomal loci (referred to as module quantitative trait loci, mQTL) that perturb the modules and describe a novel approach that integrates network properties with genetic marker information to model gene/trait relationships. Specifically, using the mQTL and the intramodular connectivity of a body weight–related module, we describe which factors determine the relationship between gene expression profiles and weight. Our approach results in the identification of genetic targets that influence gene modules (pathways) that are related to the clinical phenotypes of interest. 相似文献
94.
Two modes of germline instability at human minisatellite MS1 (locus D1S7): complex rearrangements and paradoxical hyperdeletion 下载免费PDF全文
Berg I Neumann R Cederberg H Rannug U Jeffreys AJ 《American journal of human genetics》2003,72(6):1436-1447
Minisatellite MS1 (locus D1S7) is one of the most unstable minisatellites identified in humans. It is unusual in having a short repeat unit of 9 bp and in showing somatic instability in colorectal carcinomas, suggesting that mitotic replication or repair errors may contribute to repeat-DNA mutation. We have therefore used single-molecule polymerase chain reaction to characterize mutation events in sperm and somatic DNA. As with other minisatellites, high levels of instability are seen only in the germline and generate two distinct classes of structural change. The first involves large and frequently complex rearrangements that most likely arise by recombinational processes, as is seen at other minisatellites. The second pathway generates primarily, if not exclusively, single-repeat changes restricted to sequence-homogeneous regions of alleles. Their frequency is dependent on the length of uninterrupted repeats, with evidence of a hyperinstability threshold similar in length to that observed at triplet-repeat loci showing expansions driven by dynamic mutation. In contrast to triplet loci, however, the single-repeat changes at MS1 exclusively involve repeat deletion, and can be so frequent--as many as 0.7-1.3 mutation events per sperm cell for the longest homogeneous arrays--that alleles harboring these long arrays must be extremely ephemeral in human populations. The apparently impossible existence of alleles with deletion-prone uninterrupted repeats therefore presents a paradox with no obvious explanation. 相似文献
95.
Fairclough WV Forsyth A Evans MC Rigby SE Purton S Heathcote P 《Biochimica et biophysica acta》2003,1606(1-3):43-55
We have used pulsed electron paramagnetic resonance (EPR) measurements of the electron spin polarised (ESP) signals arising from the geminate radical pair P700(z.rad;+)/A(1)(z.rad;-) to detect electron transfer on both the PsaA and PsaB branches of redox cofactors in the photosystem I (PSI) reaction centre of Chlamydomonas reinhardtii. We have also used electron nuclear double resonance (ENDOR) spectroscopy to monitor the electronic structure of the bound phyllosemiquinones on both the PsaA and PsaB polypeptides. Both these spectroscopic assays have been used to analyse the effects of site-directed mutations to the axial ligands of the primary chlorophyll electron acceptor(s) A(0) and the conserved tryptophan in the PsaB phylloquinone (A(1)) binding pocket. Substitution of histidine for the axial ligand methionine on the PsaA branch (PsaA-M684H) blocks electron transfer to the PsaA-branch phylloquinone, and blocks photoaccumulation of the PsaA-branch phyllosemiquinone. However, this does not prevent photoautotrophic growth, indicating that electron transfer via the PsaB branch must take place and is alone sufficient to support growth. The corresponding substitution on the PsaB branch (PsaB-M664H) blocks kinetic electron transfer to the PsaB phylloquinone at 100 K, but does not block the photoaccumulation of the phyllosemiquinone. This transformant is unable to grow photoautotrophically although PsaA-branch electron transfer to and from the phyllosemiquinone is functional, indicating that the B branch of electron transfer may be essential for photoautotrophic growth. Mutation of the conserved tryptophan PsaB-W673 to leucine affects the electronic structure of the PsaB phyllosemiquinone, and also prevents photoautotrophic growth. 相似文献
96.
97.
98.
99.
Humblet V Lapidus R Williams LR Tsukamoto T Rojas C Majer P Hin B Ohnishi S De Grand AM Zaheer A Renze JT Nakayama A Slusher BS Frangioni JV 《Molecular imaging》2005,4(4):448-462
Surgical resection remains a definitive treatment for prostate cancer. Yet, prostate cancer surgery is performed without image guidance for tumor margin, extension beyond the capsule and lymph node positivity, and without verification of other occult metastases in the surgical field. Recently, several imaging systems have been described that exploit near-infrared (NIR) fluorescent light for sensitive, real-time detection of disease pathology intraoperatively. In this study, we describe a high-affinity (9 nM), single nucleophile-containing, small molecule specific for the active site of the enzyme PSMA. We demonstrate production of a tetra-sulfonated heptamethine indocyanine NIR fluorescent derivative of this molecule using a high-yield LC/MS purification strategy. Interestingly, NIR fluorophore conjugation improves affinity over 20-fold, and we provide mechanistic insight into this observation. We describe the preparative production of enzymatically active PSMA using a baculovirus expression system and an adenovirus that co-expresses PSMA and GFP. We demonstrate sensitive and specific in vitro imaging of endogenous and ectopically expressed PSMA in human cells and in vivo imaging of xenograft tumors. We also discuss chemical strategies for improving performance even further. Taken together, this study describes nearly complete preclinical development of an optically based small-molecule contrast agent for image-guided surgery. 相似文献
100.
Kim S Lim YT Soltesz EG De Grand AM Lee J Nakayama A Parker JA Mihaljevic T Laurence RG Dor DM Cohn LH Bawendi MG Frangioni JV 《Nature biotechnology》2004,22(1):93-97
The use of near-infrared or infrared photons is a promising approach for biomedical imaging in living tissue. This technology often requires exogenous contrast agents with combinations of hydrodynamic diameter, absorption, quantum yield and stability that are not possible with conventional organic fluorophores. Here we show that the fluorescence emission of type II quantum dots can be tuned into the near infrared while preserving absorption cross-section, and that a polydentate phosphine coating renders them soluble, disperse and stable in serum. We then demonstrate that these quantum dots allow a major cancer surgery, sentinel lymph node mapping, to be performed in large animals under complete image guidance. Injection of only 400 pmol of near-infrared quantum dots permits sentinel lymph nodes 1 cm deep to be imaged easily in real time using excitation fluence rates of only 5 mW/cm(2). Taken together, the chemical, optical and in vivo data presented in this study demonstrate the potential of near-infrared quantum dots for biomedical imaging. 相似文献